5_6282657037939640532.pptx

US Findings of First-Trimester
Pregnancy
Sara M. Bahouth, MD, Vincenzo K. Wong, MD,
Rony V. Kampalath, MD, Jay Lin, MD,
Lori Mankowski-Gettle, MD, MBA
S.M.B. and V.K.W. contributed equally to this work.

Author Affiliations:
Department of Radiology
Baylor College of Medicine
One Baylor Plaza BCM 360
Houston, TX 77030
(S.M.B, V.K.W., R.V.K1, J.L)
Department of Radiology
University of Wisconsin School of Medicine and Public Health
Madison, Wis.
(L.M.G)
Corresponding Author:
Sara M. Bahouth, MD (e-mail: bahouth@bcm.edu).
Recipient of a Cum Laude award for an education exhibit at the 2017 RSNA Annual Meeting.
1Current address:
Department of Radiological Sciences, University of California Irvine, Orange, Calif.
Disclosures of Conflicts of Interest.—S.M.B. Activities related to the present article: disclosed no relevant relationships.
Activities not related to the present article: received money for board memberships. Other activities: disclosed no relevant
relationships.

Learning Objectives
1. Review normal embryonic development.
2. Recognize US diagnostic criteria of viable, uncertainly viable, and nonviable
intrauterine pregnancies (IUPs).
3. Diagnose ectopic pregnancy and identify its various types.
4. Distinguish between the various types of benign gestational trophoblastic disease
(GTD).

• First trimester is defined as the first 12 weeks of pregnancy
• It is a critical period when:
• 80% of miscarriages occur1
• Ectopic pregnancy occurs, which is the leading cause of maternal death2
• US plays an important role in evaluating the viability of the early pregnancy and
excluding ectopic pregnancy and GTD.
Introduction

Fertilization
Oocyte
Fertilized egg
Fertilization
Day 1 Day 2 Day 3–4
Ovulation occurs, and the
mature egg is expelled into
the fallopian tube
1
Fertilization occurs
2
Embryo divides as it
migrates to the
endometrial cavity
3

Early
blastocyst
Endometrium
Trophoblasts
Inner
cell mass
Blastocyst forms around 5 days after fertilization
and contains:
• An inner cell mass (which forms the embryo)
• Trophoblasts (which give rise to the placenta)
Day 1 Day 2 Day 3–4
Oocyte
Fertilized egg
Blastocyst Stage
Fertilization

Endometrium
Inner
cell mass
• Digest the
endometrium to
form lacunae
(blood-filled
spaces of
maternal blood)
• Produce beta-
human chorionic
gonadotropin (β-
hCG)
Syncytiotrophoblasts:
• Form chorionic villi
• Maternal blood from the lacunae bathes the chorionic villi, allowing for
exchange of nutrients, waste, and gases between mother and fetus
Cellular trophoblasts:
During implantation, trophoblasts differentiate into syncytiotrophoblasts and cellular trophoblasts.
Implantation
The blastocyst implants into the endometrium.

Early Embryologic Development
Endometrium
Inner
cell mass
Inner cell mass pulls away from the
proliferating trophoblasts.

Inner cell mass pulls away from the
proliferating trophoblasts.
An amniotic sac forms on one side.
A yolk sac forms on the other side.
Chorionic cavity surrounds the structures.
US image shows two cystic structures ( )
flanking both sides of the fetal pole ( ),
representing the yolk sac and amniotic sac.
These are surrounded by the chorionic
cavity ( ).
Endometrium
2
1
3
3
2
1
4
4
1
2
3
4
4
1
2 3

(a) US image shows the vitelline duct ( ), which is seen connecting the fetal pole ( )
to the yolk sac ( ).
(b) US image shows the amniotic sac ( ) surrounding the partially visualized fetal
pole ( ). These are surrounded by the chorionic cavity ( ). The yolk sac ( ) is also
seen.
The amnion will eventually fuse with the chorion by 14 weeks gestation, and the
chorionic cavity will obliterate.
Nonfusion of the chorion with the amnion after 14 weeks gestation is
associated with fetal/chromosomal abnormalities.
Endometrium
In early pregnancy, the vitelline duct (omphalomesenteric
duct) can be seen. This vitelline duct connects the midgut to
the yolk sac.
Failure of obliteration of the vitelline duct results in vitelline
duct remnants such as the Meckel diverticulum.
Vitelline duct
Amniotic sac
Yolk sac
Chorionic cavity
3
2
1
4
2
3
4
1
1
3
4
2
3
1 5
5
5
3
2
5 4
a. b.
3

US image shows fluid within the chorionic cavity that is
gelatinous and as such contains diffuse internal echoes ( ).
This is in contrast to the more anechoic fluid of the amniotic sac
( ).
This is considered normal and should not be mistaken for
hemorrhage.
Endometrium
2
3
4
1
Vitelline duct
Amniotic sac
Yolk sac
Chorionic cavity
3
2
1
4
4
4
2
2

Gestational sac becomes visible
(5 weeks GA)
Yolk sac becomes visible
(5.5 weeks GA)
Fetal pole and heart motion become visible
(6 weeks GA)
Embryo begins to show features and
rhombencephalon begins to form
(between 8–10 weeks GA)
Detailed anatomy
becomes more apparent
(12 weeks GA)
Yolk sac
no longer
visualized
Amnion fuses
with chorion
(14 weeks GA)
Timeline of Early Pregnancy
8-10 weeks 12 weeks and beyond
P
a
g
e
:
3
2
o
f
8
2 P
a
g
e
:
3
2
o
f
8
2
I
M
:
3
2 I
M
:
3
2
Gestational
Age (GA)
5 weeks 6 weeks 7 weeks 8 weeks 9 weeks 10 weeks 11 weeks 12 weeks 13 weeks 14 weeks
Physiologic gut herniation completes
(begins at 6–8 weeks GA and completes at 12–13
weeks GA)

Gestational sac becomes visible
(5 weeks GA)
Gestational Sac
GA 5 weeks 6 weeks 7 weeks 8 weeks 9 weeks 10 weeks 11 weeks 12 weeks 13 weeks 14 weeks
At 5–5 ½ weeks gestation, the gestational sac becomes visible.
With modern transvaginal US, any round or oval fluid collection visualized in a woman with a
positive pregnancy test likely represents an intrauterine gestation and should be reported as
such.3
It is less likely to be a decidual cyst or pseudogestational sac, which can be seen with ectopic
pregnancies.
Terms such as intradecidual sac sign and double decidual sac sign were originally used to describe findings in
the gestational sac at transabdominal US.
With the advent of transvaginal US, these signs were found to be absent in at least 35% of gestational sacs.3

Abnormal shape Irregular margins and
shape
Associated with poor
outcomes5
Small gestational sac Normal mean sac diameter
(MSD) should be greater than or
equal to 5 mm larger than the
crown rump length (CRL) at less
than 9 weeks4
MSD less than 5 mm larger than
the CRL is associated with poor
outcomes6
Thin decidual reaction Thin decidual reaction
with weakly
hyperechoic sac wall
Associated with poor
outcomes5
Gestational Sac
Abnormal Appearances of the Gestational Sac at US
US image shows a normal
gestational sac
The gestational sac should be round or oval, appear smooth and well defined, have
a decidua that is 2 mm or greater, and be positioned in the upper uterine body.4
Gestational sacs that deviate from this appearance are suspicious for abnormal
pregnancies.4

Yolk sac becomes visible
(5.5 weeks GA)
Yolk sac
no longer
visualized
Yolk Sac
The yolk sac is the next structure to appear after the gestational sac, becoming visible at approximately 5.5 weeks
GA.
The yolk sac gradually enlarges until 10 weeks GA, measuring up to 5–6 mm.
After 10 weeks, the yolk sac begins to shrink until it is no longer visualized beyond 14 weeks GA.

Absent yolk sac Abnormal in early
pregnancy if the embryo
had been present while
the yolk sac was
involuting
Generally associated with
embryonic demise9
Internal echoes within the yolk sac
anecdotally are not associated with
poor outcomes10
Differential diagnosis: calcified yolk sac
(calcified rather than echogenic
material in the yolk sac),
which is associated with failed IUP11
Echogenic yolk sac Wrinkled margins
and indented walls
Effect on outcomes is
a topic of debate, but
more recent studies
suggest no change in
outcomes10
Irregular yolk sac
Yolk Sac
Large yolk sac (> 5–6 mm)
• Associated with increased risk of demise8
Small yolk sacs visualized in very early
pregnancy (before expected shrinking after
10 weeks)
• Scant knowledge of outcomes
• Limited study showed a sac less than 2
mm is associated with poor outcomes7
• Prudent to recommend close follow-up
Small yolk sac Large yolk sac
Variable and Abnormal Appearances of the Yolk Sac at US

Yolk Sac
US image shows a single chorionic cavity
without an intervening membrane
(monochorionic).
Two yolk sacs (1, 2) are identified
(diamniotic).
Monochorionic diamniotic
US image shows two chorionic cavities
(dichorionic), which are divided by a
thick triangular-shaped membrane
(arrow). This is referred to as the twin
peak sign or lambda (λ) sign.14
Two yolk sacs are identified
(diamniotic).
Dichorionic diamniotic
US image shows two embryos ( , ).
One chorionic cavity is visualized
(monochorionic).
One yolk sac is also identified
(monoamniotic).
2
1
2
1
Monochorionic monoamniotic
Visualization of multiple yolk sacs is the earliest sign of a multigestational pregnancy.12
The number of yolk sacs matches the number of amniotic sacs if the embryos are alive.12
The first trimester is the easiest time to determine chorionicity and amnionicity of a multigestational pregnancy.13

Fetal pole and heart motion become visible
(6 weeks GA)
Fetal Heart Rate
Fetal heart motion is usually detectable around 6 weeks GA (usually visible as soon as the embryo is detectable).
The lower limit of normal for fetal heart rate (FHR) is 100 beats per minute (bpm) (at GA < 6.2 weeks) and 120 bpm
(at GA > 6.2 weeks).15
An FHR less than or equal to 90 bpm in the first trimester carries a dismal prognosis.15

M-mode is used to measure FHR.
M-mode US image displays motion along a chosen US
line. For example, the hyperechoic area ( ) on the
grayscale US image corresponds to a hyperechoic area ( )
on the M-mode image. The hypoechoic areas ( , )
on the grayscale US image correspond to the hypoechoic
areas ( , ) on the M-mode image.
The echoes encountered along the chosen US line are
mapped over time, creating the M-mode image.
At depth of , rhythmic echoes are noted, representing
movement of the beating heart ( ).
FHR is calculated by measuring the distance from trough to
trough of two subsequent waves.
FHR
Trough
Trough
1a
2a
3a
4a
1b
2b
4b
1a
1b
2a
2b
3b
4a
4a
3b
3a
3b

FHR
US Mode ISPTA (mW/cm-2)
M-mode 121
Color Doppler 344
Pulsed Doppler 1659
mW = milliwatt
Table: Comparison of Spatial Peak–Temporal-Average
Intensity (ISPTA) between US Modes18
M-mode is the preferred US mode over color and
pulsed (spectral) Doppler US.
Color and pulsed-wave Doppler US are associated with
higher power output (Table).
Although there is no evidence that color and pulsed-
wave Doppler US are harmful, all but brief insonation
is not recommended during the embryonic period.16
Spectral Doppler US should only be employed when
there is a clear benefit-risk advantage and both
thermal index (TI < 1) and examination duration are
kept low.17

US image shows that the embryo
begins to show features and
rhombencephalon begins to form
(between 8–10 weeks GA)
Fetal Rhombencephalon
The fetal rhombencephalon (which forms the medulla, pons, and cerebellum) is visible between 8 and 10 weeks GA.
It appears as a rounded anechoic structure in the posterior brain (arrow).
This is a normal finding and should not be misinterpreted as a condition.

Physiologic Herniation of Bowel
US image shows a completed physiologic gut
herniation (begins 6–8 weeks GA, completes 12–13
weeks GA)
Physiologic gut herniation occurs normally beginning from 6 to 8
weeks GA.
The bowel then undergoes a 270o counter-clockwise rotation and
returns into the abdominal cavity around 12–13 weeks GA.
This is a normal finding prior to 12–13 weeks GA and may be mistaken
for gastroschisis or omphalocele.
Amniotic
sac
Yolk
sac
Vitelline
duct
Midgut

Physiologic Herniation of Bowel19
US image shows a completed physiologic gut
herniation (begins 6–8 weeks GA, completes 12–13
weeks GA)
US findings:
• Manifests as an abdominal wall mass at the base
of the umbilical cord
• Should be 4–7 mm in a fetus with a CRL of 19–41
mm
Abnormal US findings:
• Should not be present after 12–13 weeks
• Should not be seen with a CRL greater than 44 mm
• Should be smaller than the fetal abdomen
A small echogenic mass
is visualized in the
anterior abdominal wall
(arrow), representing a
physiologic herniated
bowel.

Assessment of GA20
Determination of GA is more accurate the earlier US is performed.
• MSD measurements are not recommended for estimating due date.
• CRL is the most accurate method to establish GA (up to and including 13 6/7 weeks of gestation).
• Beyond a CRL of 84 mm (14 weeks, 0 days), dating on the basis of CRL becomes less accurate, and other second-trimester
biometric parameters should be used. These parameters (biparietal diameter, abdominal circumference, head circumference,
and femur length) are used to determine the arithmetic US age.
• At a GA of 8 6/7 weeks or less (based on last menstrual period [LMP]), US dating should be used if the LMP dating and US
dating differ by more than 5 days.
• At a GA between 9 0/7 weeks and 13 6/7 weeks (on the basis of the LMP), US dating should be used if the LMP dating and US
dating differ by more than 7 days.
• The estimated due date (EDD), if based on US dating, should be based on the earliest US examination of a CRL measurement.
Changes to the EDD should be reserved for rare circumstances.

Perigestational Hemorrhage
Perigestational hemorrhage refers to hemorrhages that occur around the fetus.
Subchorionic hemorrhages are the most common type but are not the only type.
Retroplacental hematoma (Figure A)
• Illustration (right) demonstrates a retroplacental hematoma.
• US image (left) shows a hematoma (arrow) that separates the placenta from
the uterine wall.
• The source of bleeding is probably from the spiral arteries.
• The term placental abruption is usually reserved for after 20 weeks GA.21
• Frequency of fetal demise is 50%.22
Subamniotic hematoma (Figure B)
• Illustration (right) demonstrates a subamniotic hematoma.
• US image (left) shows a hematoma (arrow) that is contained within the
amnion and chorion and extends anteriorly to the placenta, but it is limited
by the reflection of the amnion on the placental insertion site of the
umbilical cord.
• This results from the rupture of the chorionic vessels.
• This is a rare entity.
P
Chorion
Amnion
Placenta
Hematoma
P
Chorion
Amnion
Placenta
Hematoma
Placenta
A
B

(a) Illustration demonstrates a subacute marginal subchorionic
hemorrhage. P = placenta. (b) US power Doppler image shows a
collection deep relative to the chorion, with a hypoechoic fluid collection
( ) along the margin of the placenta ( ), representing a marginal
subchorionic hemorrhage. The hypoechoic appearance suggests a
subacute hemorrhage.
P
Subchorionic Hemorrhage
Acute subchorionic hemorrhage. US image (a) and color
Doppler US image (b) show a small collection deep to the
chorion that appears hyperechoic and is potentially difficult
to differentiate from the chorion. The hyperechoic
appearance suggests an acute hemorrhage.
1 2
Subchorionic hemorrhage is a frequent cause of first- and second-
trimester bleeding.
Occurs when blood collects between the chorion and uterine wall
Vaginal bleeding may occur if the blood leaks to the cervical canal.
Outcomes are dependent on the size of the subchorionic hemorrhage,
maternal age, and GA of the fetus (discussed in the next slide).
US findings:
• Crescentic collection of variable echotexture elevates the chorionic
membrane
• Echotexture varies depending on the age of the blood
• Acute: hyperechoic (may be difficult to delineate from the
chorion)
• Subacute to chronic: decreasing echogenicity over time
• May be considered a marginal subchorionic hemorrhage if the
hematoma extends to the margin of the placenta
a. b.
1
2
a. b.

Factor
Risk of Spontaneous
Abortion*
Crude Relative Risk
Size of hemorrhage
Small 7.7% 1
Medium 9.2% 1.2
Large 18.8% 2.4
Maternal age
< 35 y 7.3% 1
≥ 35 y 13.8% 1.9
GA
> 8 wk 5.9% 1
≤ 8 wk 13.7% 2.3
Note.—*Overall rate of all spontaneous abortions in this study was 9.3%.
Source.—Data are from reference 23.
US image shows a
hypoechoic collection
(arrow) that surrounds
slightly less than two-
thirds of the chorion,
representing a medium-
sized subchorionic
hemorrhage.
Subchorionic Hemorrhage The relative risk of spontaneous abortion from
subchorionic hemorrhage is dependent on the size of the
hemorrhage, maternal age, and gestational age.23
The relative risk increases with large subchorionic
hemorrhage, a maternal age of 35 years or more, and a
GA less than or equal to 8 weeks.23
In this study, the size of subchorionic hemorrhage was
defined as:
• Small: hemorrhage surrounds less than one-third of
the chorion
• Medium: hemorrhage surrounds one-third to one-
half of the chorion
• Large: hemorrhage surrounds more than two-thirds
of the chorion
Table. Subchorionic Hemorrhages and the Risk of Spontaneous Abortion

In early pregnancy, US is important to first confirm an
IUP.
Once an IUP has been confirmed, it is important to
determine the viability of the pregnancy.
It is important to distinguish between:
• Findings definitive for pregnancy failure
• Findings that are suspicious but not definitive for
pregnancy failure, which will require follow-up
testing to establish a definitive diagnosis24
Algorithm of First-Trimester Pregnancies
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
Pregnancy of
unknown
location
(PUL)
Other
GTD

In 2012, the criteria for diagnosing nonviability were
made more stringent to virtually eliminate false-positive
US results.3
In general, false-positive results at US of the first-
trimester pregnancy have worse consequences than
false-negative results.
• False-positive results:
- Diagnosing a viable pregnancy as nonviable may
result in interventions that would harm a viable IUP.
• False-negative results:
- Diagnosing a nonviable pregnancy as viable may
result in short treatment delay.
- Diagnosing an ectopic pregnancy as a PUL, which
causes a short treatment delay in a stable woman
with good follow-up, is less harmful than a false-
positive diagnosis of ectopic pregnancy, which would
harm a viable IUP.
Determining Viability
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
PUL Other
GTD

Determining Viability
Findings Diagnostic of Pregnancy Failure3
CRL ≥ 7 mm and no heartbeat
MSD ≥ 25 mm and no embryo
Absence of embryo with heartbeat ≥ 2 weeks after a US scan that showed
a gestational sac without a yolk sac
Absence of an embryo with a heartbeat ≥ 11 days after a US scan that
showed a gestational sac with a yolk sac
The criteria most often used to diagnose pregnancy failure are:
• Absence of cardiac activity by the time the embryo has
reached a certain length ( ).
• Absence of an embryo by the time a gestational sac has
grown to a certain size ( ).
• Absence of an embryo after a certain point in time ( ).
2
1
1
2
3
3a
3b

US (a) and M-mode (b) images show a CRL of 24 mm and
no heartbeat, compatible with pregnancy failure.
Pregnancy Failure
2
1
1
2
3
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IM: 58
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IM: 59
a b
3b
3a

Pregnancy Failure
2
1
1
2
3
US images show an MSD of 29.3 mm with no embryo,
compatible with pregnancy failure.
This is also referred to as an anembryonic pregnancy,
where a gestational sac forms without an embryo. This is
also sometimes referred to as a blighted ovum.
3b
3a
A B

Pregnancy Failure
1
1
2
3
2
3
a. b.
Initial US image (a) shows a gestational sac without a yolk sac.
Follow-up US image (b) obtained 2 weeks later shows a yolk sac with
absence of an embryo with a heartbeat, compatible with pregnancy
failure.
3a
3b

US image (a) obtained during an initial examination shows a
gestational sac with a yolk sac. Follow-up US image (b) obtained 11
days later shows an embryo without a heartbeat, compatible with
pregnancy failure.
Pregnancy Failure
CRL ≥7 mm and no heartbeat
• Absence of a embryo by the time a gestational sac has grown
to a certain size ( ).
1
1
2
3
2
a. b.
3b
3a

Intrauterine Pregnancy of Uncertain Viability
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
PUL Other
GTD
If an intrauterine gestational sac does not
show an embryonic heartbeat or definitive
findings of pregnancy failure, the pregnancy
is considered to be of uncertain viability.
If there is suspicion of pregnancy failure, a
follow-up US performed within 7–10 days
to reassess viability is generally
appropriate.3

IUP of Uncertain Viability
US Findings Suspicious for but not Diagnostic of Pregnancy Failure
CRL < 7 mm and no heartbeat
MSD 16–25 mm and no embryo
Absence of embryo with heartbeat 7–13 days after a US scan that showed a gestational sac
without a yolk sac
with a yolk sac
Absence of an embryo ≥ 6 weeks after last menstrual period
Empty amnion (amnion adjacent to yolk sac, no visible embryo)
Enlarged yolk sac (> 7 mm)
Small gestational sac (< 5-mm difference between MSD and CRL)
Note.—Data are from Reference 3.
The Society of Radiologists in Ultrasound consensus
findings that are suspicious for but not diagnostic of
pregnancy failure are listed in the table.
If there is any suspicion of pregnancy failure, a
follow-up US performed in 7–10 days to reassess
viability is generally appropriate.3

without a yolk sac
with a yolk sac
(a) US image of an IUP shows a CRL of less than 7
mm. (b) M-mode image shows no fetal heartbeat.
The gestational sac is also small, as demonstrated
by the large embryo in relation to the gestational
sac.
These findings are suspicious for but not
diagnostic of pregnancy failure.
a b

without a yolk sac
with a yolk sac
US image of an IUP shows an MSD (length +
height + width/3) of 16.6 mm without an embryo.
This finding is suspicious for but not diagnostic of
pregnancy failure.

CRL < 7 mm & no heartbeat
without a yolk sac
with a yolk sac
(a) US image obtained during the initial examination
shows a gestational sac without an embryo or yolk
sac. (b) Follow-up US image obtained 9 days later
shows no embryo with a heartbeat.
pregnancy failure.
a. b.

(a) US image obtained during initial examination
shows a gestational sac with a yolk sac but no
embryo. (b) Follow-up US image obtained 7 days later
shows no embryo with a heartbeat.
pregnancy failure.
without a yolk sac
with a yolk sac
a. b.

without a yolk sac
with a yolk sac
US image shows a gestational sac and amniotic
sac without an embryo, reflecting an empty
amnion.
pregnancy failure.

Findings Suspicious for but not Diagnostic of Pregnancy Failure
Crown rump length < 7 mm & no heartbeat
Mean sac diameter 16-25 mm and no embryo
Absence of embryo with heartbeat 7-13 days after a scan that showed a gestational sac
without a yolk sac
Absence of embryo with heartbeat 7-10 days after a scan that showed a gestational sac
with a yolk sac
US image shows a large yolk measuring
greater than 7 mm, which is suspicious for
but not diagnostic of pregnancy failure.

Retained Products of Conception
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
PUL Other
GTD
RPOC
present
RPOC
absent
When evaluating for passage of a nonviable fetus, it is important
to evaluate for retained products of conception (RPOC).
The presence of RPOC differentiates a complete miscarriage
(no RPOC present) from an incomplete miscarriage (RPOC
present).
Patients with RPOC often present with postpartum hemorrhage.25
RPOC occurs more frequently in cases of medical termination of
pregnancy and second-trimester miscarriage.25
Treatment includes the administration of prostaglandin E1
analogs, dilation and curettage, or hysteroscopic removal.

Gray-scale transverse (a) and
longitudinal (b) US images of a
postpartum patient show a
thickened EEC (arrows).
This is seen on both transverse and
longitudinal images, confirming the
masslike nature of the structure.
RPOC a.
b.
Gray-scale US findings:
• Thickened endometrial echocomplex (EEC)
• Most sensitive finding for RPOC
• Using 10-mm cutoff
• 80% sensitivity
• 20% specificity
• 63%–80% negative predictive value (NPV) if EEC is less than 10 mm25
• Endometrial mass
• Defined as a structure seen in two orthogonal planes, separate from the
endometrium
• Sensitivity: 29%–79%
• High positive predictive value (PPV, 80%)25

Mild vascularity
Moderate vascularity
Marked vascularity
No vascularity
RPOC
No RPOC RPOC
EEC < 10 mm
(NPV 63%–80%)
EEC > 10 mm
Sensitive (80%), not specific (20%)
No endometrial mass
NPV 85%–95%
Endometrial mass
Less sensitive (29%–79%), more specific
PPV 80%
No vascularity
NPV 88%–95%
Absence of all findings (PPV 100%)
Vascularity
Combination of vascularity with thickened stripe or
endometrial mass (PPV 96%)
Color Doppler US findings:
• Presence of flow in a thickened endometrium or endometrial mass is highly predictive (PPV, 96%)25
• Absence of flow does not exclude products of conception (POC; can represent clot or avascular
POC)26
• Avascular POC will probably pass without intervention25
• Markedly vascular POC has a risk of severe bleeding during dilation and curettage, which may be
secondary to mistakenly unroofing a large vessel. As such, the obstetrician should be notified.25

Color Doppler US image of a
postpartum patient shows marked
vascularity extending from the
myometrium to the endometrium,
suggesting RPOC.
RPOC
Differential diagnosis:
• Arteriovenous malformation (AVM)
• Usually post-traumatic (dilation and curettage)
• AVM: vascularity centered in the myometrium at US
• RPOC: vascularity centered in the endometrium at US
• Subinvolution of the placental implantation site
• Rare
• Uterine vessels fail to involute after delivery
• May appear as dilated myometrial vessels at US25
• Nonobstetric condition (polyps, fibroids)
• GTD
• β-hCG levels remain elevated (β-hCG levels should decline with RPOC)

Ectopic Pregnancy
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
PUL Other
GTD
Ectopic pregnancy is the most common cause of
pregnancy-related maternal mortality in the first
trimester.27
Initial evaluation consists of performing hormonal
assays and pelvic US.
Pelvic pain with an abnormal β-hCG level should
trigger evaluation for an ectopic pregnancy.

Overall incidence: 1%–2% of pregnancies27
Prevalence was thought to be increasing owing to the use
of assisted reproductive technology (ART), although it is
currently declining, possibly from evolving ART
techniques.28
Risk factors
• Prior ectopic pregnancy
• Tubal injury
• Pelvic inflammatory disease
• Salpingitis isthmica nodosa
• Endometrial injury or congenital anomalies
• Intrauterine device (IUD) use
ART30
Natural Conception29
Ovarian
3.2%
Fimbrial
11.1%
Ampullary
70%
Isthmus
12%
Interstitial
2.4%
Interstitial
2.5%
Tubal
~ 95%
Tubal
90%– 95%
Ovarian/abdominal
4.3%
Abdominal
1.3%
Cervical
<1%
Cervical
<1%
Heterotopic30
1%–3 %
Heterotopic
1 in 30,000
Ectopic Pregnancy
Frequency of Ectopic Pregnancy Sites
Isthmus
5%– 10%
Ampullary
80%

• 95% of ectopic pregnancies are located in the fallopian tube.27
• Most common finding is an adnexal mass, which is separate from the ovary
(seen in 89%–100% of patients). An adnexal mass may not be detected at
transvaginal US in 15%–35% of patients.27
• Second most common finding is a “ring of fire” sign, which is seen as
peripheral hypervascularity on color Doppler US images. This is a nonspecific
finding and can be seen with corpus luteal cysts. Thus, the sign is useful after
confirming the ring of fire in an adnexal mass outside of the ovary. 27
• Echogenic fluid within the Morrison pouch and the cul-de-sac should raise
concern for a ruptured ectopic pregnancy. In a patient with positive β-hCG
levels, echogenic fluid is predictive for ectopic pregnancy, with an 86%–93%
PPV.31
• Absence or presence of free fluid is not a reliable indicator to exclude a tubal
rupture, according to one study.32
• 21% of cases of tubal rupture were found to have no fluid or trace free
fluid
• 37% of patients with free fluid in the right upper quadrant were found
to have intact fallopian tubes
Ectopic Pregnancy:
Tubal Ectopic Pregnancy
Page: 80 of 95
Page: 80 of 95 IM: 92
IM: 92
a. b.
c. d.
US (a) and color Doppler US (b–d) images show a large complex mass in
the right adnexum. Within this mass is an area of peripheral vascularity,
representing the ring of fire sign ( in b), which helps confirm an ectopic
pregnancy. The ring of fire sign is surrounded by an avascular area that
represents a clot that extruded from the fallopian tube during surgery.
The mass is adjacent to the right ovary (c), which also contains a corpus
luteal cyst that shows peripheral vascularity. A small amount of complex
fluid that contains internal echoes is noted adjacent to the right adnexal
mass ( in d), concerning for ruptured ectopic pregnancy.
2
1
1
2

(a) Longitudinal US image of the uterus (a) shows complex fluid
within the posterior cul-de-sac ( ), as well as an IUD within the
endometrial cavity.
(b, c) US images show a thick walled cystic structure in the left
adnexum, which appears separate from the left ovary (arrow in c).
Overall, the findings are highly concerning for a ruptured ectopic
pregnancy with hemoperitoneum.
Whenever hemoperitoneum is present, additional views should be
obtained in the right and left upper quadrants to evaluate the extent
of hemorrhage.
(d) US image from an additional evaluation of the right upper
quadrant shows fluid in the hepatorenal recess, concerning for a
large volume of hemoperitoneum.
Ectopic Pregnancy:
Tubal Ectopic Pregnancy
a. b.
c. d.
1
1

If it is unclear if the mass is separate from the ovary, consider a
technique that uses a combination of US transducer pressure
with stomach palpation to evaluate the movement of the two
structures.
Movement of the structure in question as one with the ovary
 suggests mass is within the ovary
Movement of the structure in question separate from the ovary
 suggests mass is outside the ovary
Ectopic Pregnancy:
Differentiating Ovarian from Adnexal
US cine clip shows the right adnexum with a
combination of US transducer pressure and
palpation of the stomach.
A complex mass was shown to move as one with
the ovary, suggesting the lesion was ovarian in
origin and likely a hemorrhagic corpus luteum
rather than an ectopic pregnancy.

• Uncommon
• Occurs when implantation takes place within the intramyometrial segment
of the fallopian tube
• Can manifest later (up to 16 weeks GA) owing to distensibility of this
segment33
• Accounts for almost 20% of deaths caused by hemorrhage in ectopic
pregnancies, despite an incidence of 2%–6% of ectopic pregnancies
• Sometimes used interchangeably with the term cornual ectopic pregnancy,
which technically refers to implantation within the cornua of a bicornuate
or septate uterus
• Findings:
• Eccentrically located sac surrounded by thin myometrium (< 5 mm)27
• Interstitial line sign (a thin echogenic line connecting the
endometrium to the gestational sac, representing the interstitial
portion of fallopian tube) (80% sensitive, 98% specific)34
Ectopic Pregnancy
Ectopic Pregnancy:
Interstitial Ectopic Pregnancy
(a) Illustration shows the gestational sac within the intramyometrial
portion of the fallopian tube.
(b, c) Longitudinal (b) and transverse (c) color Doppler US images of the
uterus show a gestational sac that appears separate from the fundal
endometrium. Both appear connected by an echogenic line (arrows in b),
representing the interstitial line sign. The gestational sac appears eccentric
and surrounded by a thin layer of myometrium ( in c).
b. c.
US cine clip of an interstitial
pregnancy shows a round
gestational sac that appears
separate from the endometrium.
There is associated fluid within
the endometrial cavity.
a.
1
1

Ectopic Pregnancy
• Uncommon
• Must be distinguished from a miscarriage in progress
• US findings:
• Hourglass appearance of uterus as fetus expands the cervix35
• Cardiac activity below the internal os35
• Differential diagnosis:
• Miscarriage in progress
• Gestational sac may be noted to change shape or location during or between
US examinations
• Sliding sign: if US transducer can manipulate the gestational sac, it suggests
nonadherence to the cervix36
• Cesarean scar ectopic pregnancy
• Gestational sac in anterior myometrium, with overlying myometrial defect27
• May also rupture from myometrial thinning along the cesarean scar
Ectopic Pregnancy:
Cervical Ectopic Pregnancy
Cervical ectopic pregnancy. (a) Transverse US
image of the cervix shows a gestational sac with a
yolk sac. (b) Three-dimensional US image shows
the gestational sac below the internal os (arrows).
Miscarriage in
progress. Longitudinal
US image of the
uterus shows a
flattened irregular
gestational sac
(arrow).
Cesarean scar ectopic
pregnancy. Longitudinal
US image of the uterus
shows a gestational sac
at the site of a cesarean
delivery scar with
overlying myometrial
defect (arrow).
a. b.

Ectopic Pregnancy
• Ovarian ectopic pregnancy
• Accounts for 3% of ectopic pregnancies
• May be a part of a heterotopic pregnancy
• Strongly associated with use of an IUD
• May be suggested by the presence of a gestational sac, chorionic villi, or an atypical cyst with hyperechoic ring with a normal
fallopian tube
• Abdominal ectopic pregnancy
• Accounts for 1.3% of ectopic pregnancies
• Occurs within the intraperitoneal cavity
• Significant risk of hemorrhage with maternal mortality is 7.7 times greater than other ectopic pregnancy locations
• Heterotopic pregnancy
• Rare in the general population (1 in 30,000)
• Represents coexistence of an IUP and ectopic pregnancy
• Not uncommon in patients undergoing in vitro fertilization (IVF) (1%–3% of all pregnancies)
• Note that the rate of heterotopic pregnancies in the IVF population (1%–3%) is similar to that of all ectopic pregnancies in the
general population (1%–2%). Thus, careful examination should occur in the IVF population to evaluate for heterotopic
pregnancies.
Ectopic Pregnancy:
Additional Types37

Pregnancy of Unknown Location
One proposed classification scheme for uniformity in categorizing the location of pregnancy is listed above.
Extrauterine
gestational sac
+
yolk sac and/or embryo
Definite
Ectopic Pregnancy
Inhomogeneous
adnexal mass
or
extrauterine saclike
structure
Probable
Ectopic Pregnancy
No signs of intrauterine
or extrauterine
gestation at
transvaginal US
PUL
Intrauterine echogenic
saclike structure
Probable
IUP
Intrauterine
gestational sac
+
Definite
IUP
Classification of US Findings38

PUL
Extrauterine
gestational sac
+
Definite
Ectopic Pregnancy
Inhomogeneous
adnexal mass
or
extrauterine saclike
structure
Probable
Ectopic Pregnancy
No signs of intrauterine
or extrauterine
gestation at
transvaginal US
PUL
Intrauterine echogenic
saclike structure
Probable
IUP
Intrauterine
gestational sac
+
Definite
IUP
Classification of US Findings38
When the location of a pregnancy cannot be determined (no intrauterine fluid collection and normal/near-normal adnexa), this is
considered a PUL. Near-normal adnexa includes the corpus luteum, small amount of pelvic free fluid, and a paratubal cyst.3
When pregnancy location cannot be established, it is important to understand the role of β-hCG in determining management.

Weeks of pregnancy
β-hCG
levels
(mIU/mL)
Table 1. β-hCG Levels during Pregnancy
0
50,000
100,000
150,000
200,000
250,000
300,000
350,000
1 2 3 4 5 6 7-8 9-12 13-16 17-24 25-40
range of normal
Review of β-hCG
Table 2. Serial β-hCG levels
Level of β-hCG Indication
Rising
Normal
(> 50% in 48 hours)
Supports diagnosis of viable IUP
21% of ectopic pregnancies show normal doubling
times
Abnormal
(< 50% in 48 hours)
Almost certainly a nonviable pregnancy (intrauterine
or extrauterine)
Early plateau Highly suggestive of ectopic pregnancy
Decreasing
Most consistent with failed pregnancy
(including miscarriage, spontaneously resolving
ectopic pregnancy)
• β-hCG levels peak at 9–11 weeks, after which they decline (Table 1)
• The average doubling time of β-hCG levels in a normal viable IUP is
approximately 48 hours (range 1.2 – 2.2 days) (Table 2)
• A less than 50% rise in 48 hours is almost always a nonviable
pregnancy (intrauterine or extrauterine)39
• Ectopic pregnancies may manifest with abnormal rise, fall, or early
plateau of β-hCG levels
• β-hCG level is not always reliable
• 1% with viable IUP show slower doubling time40
• 21% of ectopic pregnancies show normal doubling times41
• Thus, evaluation is made with a combination of β-hCG levels and
US

Weeks of pregnancy
β-hCG
levels
(mIU/mL)
Table 1. β-hCG Levels during Pregnancy
0
50,000
100,000
150,000
200,000
250,000
300,000
350,000
1 2 3 4 5 6 7-8 9-12 13-16 17-24 25-40
range of normal
Review of β-hCG
• The use of a discriminatory zone (orange in Table 1), a defined single β-hCG
level in which a gestational sac should be visualized at US, has been widely
investigated. Some define this value up to 3500 mIU/mL.42
• Because of considerable overlap of β-hCG values among viable IUP, non-
viable IUP, and ectopic pregnancies, a single β-hCG measurement cannot
reliably establish the location of a pregnancy.3
• For example, in a patient with a β-hCG level of 2000–3000 mIU with
no gestational sac at US, an ectopic pregnancy is 19 times more likely than
an IUP. However, there is a 2% chance of viable IUP.3
• The use of a single β-hCG and discriminatory zone may be used as an aid to
guide management in terms of follow-up but should not be used as an
indication for initiating treatment for ectopic pregnancy.
Table 2. Serial β-hCG levels
Level of β-hCG Indication
Rising
Normal
(> 50% in 48 hours)
Supports diagnosis of viable IUP
21% of ectopic pregnancies show normal doubling
times
Abnormal
(< 50% in 48 hours)
Almost certainly a nonviable pregnancy (intrauterine or
extrauterine)
Early plateau Highly suggestive of ectopic pregnancy
Decreasing
Most consistent with failed pregnancy
(including miscarriage, spontaneously resolving ectopic
pregnancy)

• Differential diagnosis of PUL includes an early IUP, failed pregnancy, or ectopic pregnancy.
• Management of PUL varies considerably.
• Follow-up β-hCG level tests and/or US are recommended in a stable patient who desires the pregnancy.42
• Other tests include progesterone levels, biomarker levels, the use of mathematical models, and endometrial aspiration in certain situations to
guide management.
PUL
No signs of intrauterine or
extrauterine gestation at
transvaginal US
PUL
IUP
Ectopic pregnancy
Resolved PUL
Persisting PUL
Potential outcomes37
Follow-up β-hCG
level testing
and/or US

GTD encompasses benign and malignant forms.
All GTDs arise from the placenta.43
Hydatidiform moles and choriocarcinoma arise from
cellular (villous) trophoblasts.43
+β-hCG
Viable
IUP
IUP of
uncertain
viability
Nonviable
Nonviable
IUP
Complete
miscarriage
Incomplete
miscarriage
Ectopic
pregnancy
PUL Other
GTD
Endometrium
Inner
cell
mass
• Digest the
endometrium to
form lacunae
• Produce β-hCG
Syncytiotrophoblasts
• Form chorionic villi
Cellular trophoblasts
GTD

GTD
Benign
Complete molar
pregnancy
Partial
molar pregnancy
Malignant
Invasive mole Choriocarcinoma
Placental site
trophoblastic
tumor
Epithelioid
trophoblastic
tumor
15%–20% progress to
gestational
trophoblastic neoplasia
High β-hCG levels
β-hCG levels greater
than 100,000 mIU/mL in
50% of patients41
< 5% progress to
gestational
trophoblastic neoplasia
High β-hCG levels
β-hCG levels greater
than 100,000 mIU/mL in
less than 10% of
patients41
0.5–1/1000 pregnancies in
North America and Europe
GTD

• Often diagnosed early because of routine US and β-hCG testing
• 58%–95% detection at US44
• US findings:
• Large-for-date uterine size
• Snowstorm appearance of the endometrium (echogenic mass with hypoechoic foci)
• Small (1–30 mm) cysts of varying sizes in the endometrium (representing hydropic
chorionic villi and described as a “cluster of grapes”)
• Theca lutein cysts (in 20%), representing large functional ovarian cysts that enlarge
the ovaries, may occur secondary to exaggerated ovarian stimulation by the high
levels of β-hCG.
GTD:
Complete Molar Pregnancy
46, XX
46, XY
or XX
Empty
ovum
Empty
ovum
Dispermy
Chromosome
duplication
Genetics of a Complete Mole
(a) Longitudinal US image of the endometrium shows a
thick endometrial mass with cystic spaces representing
a complete mole. (b) Longitudinal US image of an
ovary shows an enlarged ovary with large cysts
compatible with theca lutein cyst.
a. b.

Gestational Trophoblastic Disease
• False-negative results are common (17%–29% detection at US)44
• Can mimic anembryonic pregnancy, miscarriage, or RPOC
• Given the difficulty in detection, correlation with quantitative β-hCG levels is key
• US findings:
• Gestational sac may appear empty, elongated, or ovoid or contain
amorphous echoes (fetal parts)
• Fetal demise, anomalies, growth restriction
• Oligohydramnios
• Enlarged placenta relative to size of the uterus with cystic change (“Swiss
cheese” appearance)
GTD:
Partial Molar Pregnancy
Longitudinal color Doppler US image of the uterus shows
an enlarged placenta with cystic changes (arrows), giving
a Swiss cheese appearance.
69,
XXX, XXY,
or XYY
23, X
Dispermy
Genetics of a Partial Mole

• In early pregnancy, US is important to confirm location of a pregnancy.
• Once an IUP has been confirmed, fetal viability must be determined.
• For IUPs, it is important to distinguish between sonographic findings that are definitive for pregnancy failure and those that are suspicious for but not
definitive of pregnancy failure, which require follow-up testing to establish a definitive diagnosis.
• If an IUP has not been confirmed and an ectopic pregnancy is suspected on the basis of the results of laboratory examinations, then an extended search
must be performed.
• Most ectopic pregnancies occur in the fallopian tube and most commonly manifest as an adnexal mass.
• PUL is considered when there are no signs of intrauterine or extrauterine gestation.
• β-hCG level is used to help determine fetal viability. A greater than 50% rise over 48 hours suggests a viable IUP. A less than 50% rise over 48 hours
suggests a nonviable pregnancy (either intrauterine or extrauterine).
• In miscarriages, the presence of RPOC differentiates a complete miscarriage (RPOC absent) and an incomplete miscarriage (RPOC present).
• A combination of endometrial thickening, an endometrial mass, and vascularity is highly predictive for RPOC.
• A complete mole may be seen as an intrauterine mass with cystic spaces without any associated fetal parts. In comparison, a partial mole may manifest
as a gestational sac containing amorphous echoes representing fetal parts.
• Less than 50% of all hydatidiform moles are detected at US, mostly owing to difficulty in detecting partial moles, which can be mistaken for anembryonic
pregnancy, miscarriage, or RPOC. Correlation with β-hCG levels is key.
Summary

Suggested Readings
Doubilet PM. Ultrasound evaluation of the first trimester. Radiol Clin North Am 2014;52(6):1191–1199.
Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria for nonviable pregnancy early in the first
trimester. N Engl J Med 2013;369(15):1443–1451.
Lin EP, Bhatt S, Dogra VS. Diagnostic clues to ectopic pregnancy. RadioGraphics 2008;28(6):1661–1671.
Sellmyer MA, Desser TS, Maturen KE, Jeffrey RB Jr, Kamaya A. Physiologic, histologic, and imaging
features of retained products of conception. RadioGraphics 2013;33(3):781–796 .
Shaaban AM, Rezvani M, Haroun RR, et al. Gestational trophoblastic disease: clinical and imaging
features. RadioGraphics 2017;37(2):681–700.

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